April 8, 2020

expert comment about measuring the immune antibody response to COVID-19 infection in patients

There have been questions from journalists about measuring the level of immune response to infection in patients with COVID-19.

Prof Gabriel Leung, Helen and Francis Zimmern Professor in Population Health, and Chair of Public Health Medicine, University of Hong Kong, said:

“We need to tease out what the antibody response means.  There are two things – one is to look at the severity of illness; what kinds of patients they are, their age profile, and what stage of illness or recovery they may be in.  All of the above would affect the antibody titre.  Secondly, what kind of antibody test has one used to detect those titres – is it the screening ELISA; is it the neutralisation tests?  They can be very tricky – especially the neutralisation tests.  So one has to be very careful trying to make inferences based on reports that are number 1 not fully written up and documented, so that it is clear for all to discern all these factors; and number 2, through peer review.

“General comments I can make based on data I have seen both from Hong Kong and elsewhere is that it tracks the severity of illness.  So younger people who tend not to get quite as sick as older folks generally tend not to mount as high an antibody titre response as those who may be older.

“Secondly more generally, people who have milder symptoms and a milder course of illness tend again not to mount as robust a response in terms of the antibodies.

“Thirdly, it depends on whether you are looking at the acute phase – usually we look at IgM for the acute phase – or you are looking at the longer term IgG, which doesn’t really go high or stay high until a week or two or three after the infection event itself.

“What everybody is really waiting for is large scale studies that have got data on viral shedding (the quantitative PCR), and virus isolation of at least some of those virus samples – because sometimes, even though you may still shed, the virus is actually not a live virus and therefore not infectious.  The third thing you may wish to track longitudinally through illness is the various different antibody responses.  Ideally you would have all three on a daily or every other day basis from the time of first diagnosis and then you follow them through their illness and recovery, and then follow them long term so that you can determine how stable their antibody response may be and for how long it might last, which then goes to the possibility of herd immunity, if we have had one or two or three waves of this COVID-19 sweeping through the population and therefore you may then, before you actually get wide access to an effective vaccine, you could hopefully try to mitigate the pandemic a little bit.

“So there are a lot of unknowns at the moment.  What I have described here only applies to the people that have been identified as patients – what is perhaps even more important is to have very good age-stratified population sero-surveys to look at what is actually happening out there which will in large part inform what the shape and size of the clinical iceberg is.  We can only see what is above the observation threshold – we can’t see what is below the observation threshold, those people who never come to seek care or who never can access care because the health system has exceeded its surge capacity.”

All our previous output on this subject can be seen at this weblink: www.sciencemediacentre.org/tag/covid-19

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